Another interesting study, look where it states that the hypothalamos is involved in erections. By getting N-methyl-D-aspartic acid into this part of the brain, triggers erections.
Lack of central nitric oxide triggers erectile dysfunction in diabetes
Hong Zheng,1 Keshore R. Bidasee,2 William G. Mayhan,1 and Kaushik P. Patel1
Erectile dysfunction is a serious and common complication of diabetes mellitus. The proposed mechanisms for erectile dysfunction in diabetes include central and autonomic neuropathy, endothelial dysfunction, and smooth muscle dysfunction. The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in centrally mediated penile erection. This study was designed to examine the role of nitric oxide (NO) within the central nervous system component of the behavioral responses including erection in diabetic rats. N-methyl-D-aspartic acid (NMDA)-induced erection, yawning, and stretch through the PVN can be blocked by prior administration of NO synthase (NOS) blocker, L-NMMA, in freely moving, conscious male normal rats. Four weeks after streptozotocin (STZ) and vehicle injections, NMDA-induced erection, yawning, and stretch responses through the PVN are significantly blunted in diabetic rats compared with control rats. Examination of neuronal NOS (nNOS) protein by Western blot analysis indicated a reduced amount of nNOS protein in the PVN of rats with diabetes compared with control rats. Furthermore, restoring nNOS within the PVN by gene transfer using adenoviral transfection significantly restored the erectile and yawning responses to NMDA in diabetic rats. These data demonstrate that a blunted NO mechanism within the PVN may contribute to NMDA-induced erectile dysfunction observed in diabetes mellitus.
neuronal nitric oxide synthase; sexual dysfunction; behavioral responses
ERECTILE DYSFUNCTION IS A serious and common complication of diabetes mellitus (12, 32). The proposed mechanisms for erectile dysfunction in diabetes include central and autonomic neuropathy, endothelial dysfunction, and smooth muscle dysfunction (13, 20). The coexistence of the neuropathic and angiopathic changes in the vast majority of diabetic patients (and in an array of experimental animal models) has complicated efforts to define their relative contributions to erectile dysfunction (20, 31). Thus, the precise pathophysiological mechanisms of erectile dysfunction in diabetic patients remain obscure.
In diabetic male patients Sildenafil (Viagra) appears to be therapeutic in 50% of the patients (4, 17). This suggests that there is another mechanism that may be important in erectile dysfunction in diabetic males. Apart from the peripheral actions of corporal smooth muscle relaxation, erectile dysfunction is related to a complex interaction between sensory and autonomic fibers (1). Penile erection is thought to involve parasympathetic, neuronally mediated relaxation of blood vessels, as well as of the trabecular meshwork of smooth muscle that comprises the corpora cavernosa (1, 16). The activation of parasympathetic nerves involves central mechanisms responsible for penile erection, and the subsequent vasodilation that results involves underlying peripheral mechanisms. Erectile dysfunction is thought to involve the central nervous system component of this pathway.
The paraventricular nucleus (PVN) of the hypothalamus is an integration center between the central and peripheral autonomic nervous systems. It is involved in numerous functions from feeding, metabolic balance, blood pressure, and heart rate, to erectile function and sexual behavior. Some premotor neurons that project into the spinal proerectile neurons are present in the PVN of the hypothalamus (36).
Nitric oxide (NO) plays an important role in normal penile erection by virtue of its ability to potently relax corporal smooth muscle cells in the penis (1). In addition to this well-documented peripheral action, evidence is accumulating that indicates NO may also function as a neurotransmitter in the central nervous system to modulate sexual behavior and penile erection (15, 21). The PVN is a primary site within the forebrain that has been implicated in NO-mediated penile erection (9, 30). Delivering NO or NO donors to the PVN of conscious rats elicits episodes of penile erection and yawning (21), and electrical stimulation of the PVN in anesthetized rats elicits an increase in intracavernous pressure (8).
Penile erection, yawning, and stretch are behavioral responses that occur concomitantly in response to the administration of N-methyl-D-aspartic acid (NMDA) within the PVN (22). NMDA receptor activation causes an influx of calcium, which, in turn, is associated with the activation of NO synthase (NOS), resulting in the synthesis/release of NO. Nitric oxide plays an important role in the expression of penile erection and yawning (21). Consistent with these observations, blockade of NOS with NG-monomethyl-L-arginine (L-NMMA) prevented NMDA-induced erection (22).
The present study was designed to examine NMDA/NO-induced penile erection, yawning, and stretch in streptozotocin (STZ)-induced diabetic rats. We hypothesized that the blunted behavioral responses to NMDA in diabetes reflects an impaired NO mechanism within the PVN. The involvement of NO mechanism in the NMDA-mediated behavioral response was also explored, as was the possibility that diabetes impairs the transduction of changes in NO-mediated behavioral responses.
